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Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in Lipid Nanoparticle (LNP)

RNA-based vaccine represents an irresistible and safe immunization strategy with decreasing theoretical risks of genomic integration and malignant cell transformation. To our knowledge, however, there is no report about development of RNA vaccine against Toxoplasma gondii infection. We have previous...

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Autores principales: Luo, Fangjun, Zheng, Lina, Hu, Yue, Liu, Shuxian, Wang, Yan, Xiong, Zhongkui, Hu, Xin, Tan, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380742/
https://www.ncbi.nlm.nih.gov/pubmed/28424680
http://dx.doi.org/10.3389/fmicb.2017.00605
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author Luo, Fangjun
Zheng, Lina
Hu, Yue
Liu, Shuxian
Wang, Yan
Xiong, Zhongkui
Hu, Xin
Tan, Feng
author_facet Luo, Fangjun
Zheng, Lina
Hu, Yue
Liu, Shuxian
Wang, Yan
Xiong, Zhongkui
Hu, Xin
Tan, Feng
author_sort Luo, Fangjun
collection PubMed
description RNA-based vaccine represents an irresistible and safe immunization strategy with decreasing theoretical risks of genomic integration and malignant cell transformation. To our knowledge, however, there is no report about development of RNA vaccine against Toxoplasma gondii infection. We have previously demonstrated that the recombinant T. gondii nucleoside triphosphate hydrolase-II (NTPase-II) protein is able to provide protective Th1 cell-mediated immunity against T. gondii. Herein, we evaluated the immunogenic potential of a self-amplifying RNA vaccine-encoding T. gondii NTPase-II gene, RREP-NTPase-II, delivered by a synthetic lipid nanoparticle (LNP). Immunization of mice with naked RREP-NTPase-II induced a strong cellular and humoral immune response with high-IgG antibody titers and IFN-γ production. The immunized mice displayed significantly prolonged survival time and reduction in brain parasite load (46.4%) compared with control group. Furthermore, mice vaccinated with RREP-NTPase-II-encapsulated LNP displayed significantly enhanced protection against acute infection as well as chronic infection with PRU cyst, which shows 62.1% reduction in brain cyst burden in comparison to control group. These results suggest that the combination of self-amplifying RNA and LNP ion would be beneficial to the development of a safe and long-acting vaccine against toxoplasmosis.
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spelling pubmed-53807422017-04-19 Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in Lipid Nanoparticle (LNP) Luo, Fangjun Zheng, Lina Hu, Yue Liu, Shuxian Wang, Yan Xiong, Zhongkui Hu, Xin Tan, Feng Front Microbiol Microbiology RNA-based vaccine represents an irresistible and safe immunization strategy with decreasing theoretical risks of genomic integration and malignant cell transformation. To our knowledge, however, there is no report about development of RNA vaccine against Toxoplasma gondii infection. We have previously demonstrated that the recombinant T. gondii nucleoside triphosphate hydrolase-II (NTPase-II) protein is able to provide protective Th1 cell-mediated immunity against T. gondii. Herein, we evaluated the immunogenic potential of a self-amplifying RNA vaccine-encoding T. gondii NTPase-II gene, RREP-NTPase-II, delivered by a synthetic lipid nanoparticle (LNP). Immunization of mice with naked RREP-NTPase-II induced a strong cellular and humoral immune response with high-IgG antibody titers and IFN-γ production. The immunized mice displayed significantly prolonged survival time and reduction in brain parasite load (46.4%) compared with control group. Furthermore, mice vaccinated with RREP-NTPase-II-encapsulated LNP displayed significantly enhanced protection against acute infection as well as chronic infection with PRU cyst, which shows 62.1% reduction in brain cyst burden in comparison to control group. These results suggest that the combination of self-amplifying RNA and LNP ion would be beneficial to the development of a safe and long-acting vaccine against toxoplasmosis. Frontiers Media S.A. 2017-04-05 /pmc/articles/PMC5380742/ /pubmed/28424680 http://dx.doi.org/10.3389/fmicb.2017.00605 Text en Copyright © 2017 Luo, Zheng, Hu, Liu, Wang, Xiong, Hu and Tan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Luo, Fangjun
Zheng, Lina
Hu, Yue
Liu, Shuxian
Wang, Yan
Xiong, Zhongkui
Hu, Xin
Tan, Feng
Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in Lipid Nanoparticle (LNP)
title Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in Lipid Nanoparticle (LNP)
title_full Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in Lipid Nanoparticle (LNP)
title_fullStr Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in Lipid Nanoparticle (LNP)
title_full_unstemmed Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in Lipid Nanoparticle (LNP)
title_short Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in Lipid Nanoparticle (LNP)
title_sort induction of protective immunity against toxoplasma gondii in mice by nucleoside triphosphate hydrolase-ii (ntpase-ii) self-amplifying rna vaccine encapsulated in lipid nanoparticle (lnp)
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380742/
https://www.ncbi.nlm.nih.gov/pubmed/28424680
http://dx.doi.org/10.3389/fmicb.2017.00605
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